The role of natural killer cell receptors in the control of natural killer cell functions
Bibliographic record
Abstract
Natural killer (NK) cells possess the ability to destroy abnormal cells such as cancerous and virally-infected cells. A common feature of these cells is the downregulation of class I MHC molecules in an attempt to evade recognition by CD8+ T lymphocytes. "Missing-self" recognition allows NK cells to identify and destroy cells with decreased MHC-I expression. MHC-I receptors are expressed by NK cells, therefore allowing "missing-self" recognition. The major MHC-I receptors on human NK cells are KIR while mouse NK cells express Ly49 receptors. In addition to the recognition of MHC-I on target cells, Ly49 receptors are also involved in the education of NK cells, a process in which developing NK cells acquire effector functions.In human, KIR haplotypes vary greatly between individuals and the same phenomenon is observed in mice; Ly49 haplotypes differ in various mouse strains. Sequencing of the non-obese diabetic (NOD) Ly49 haplotype revealed that this strain encodes for the largest Ly49 haplotype known to date. The NOD Ly49 cluster is characterized by the largest number of genes coding for activating Ly49 receptors. The presence of a large number of Ly49 activating receptors may affect NK cell activation status and influence the development of diabetes in NOD mice.To gain insight in the in vivo role of Ly49 receptors in the control of NK cell activity, a NKC-knockdown mouse was generated. NK cells from these mice show greatly decreased expression of NKC-encoded receptors such as Ly49. NKC-knockdown NK cells have reduced lysis of MHC-I-negative target cells in vitro and in vivo. The ability of NK cells to destroy MHC-I-negative cells is restored by the re-introduction of a single Ly49 receptor. These results provide the first direct evidence that Ly49 receptors are involved in the in vivo surveillance of MHC-I molecules. Interestingly, the absence of Ly49 receptors results in defective "missing-self" recognition but activation of NK cells by MHC-I-independent mechanisms is not impaired.NKR-P1 receptors, which bind to Clr proteins, are members of another receptor family expressed by NK cells. Interestingly, the genes coding for NKR-P1 and Clr ligands are located in the same cluster and are therefore inherited together. Previous analyses demonstrated that the Nkrp1-Clr gene cluster is conserved in B6 and BALB/c mice. Mapping of the 129-strain cluster confirmed the high degree of conservation of the Nkrp1-Clr gene order in 129-strain mice. Gene sequencing revealed conservation of 129 and BALB/c Nkrp1 and Clr genes and divergence from the B6 genes, suggesting that the 129 cluster is more closely related to the BALB/c cluster than to the B6 cluster.Taken together, the Ly49 receptor family varies greatly in contrast with the highly conserved NKR-P1 receptors. Loss of Ly49 receptor expression reveals that Ly49 receptors are required for the acquisition of "missing-self" responses by NK cells.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".